̽��ֱ�� of Cambridge - vaccine

Incidence of heart attacks and strokes was lower after COVID-19 vaccination

cjb250 — Wed, 31 Jul 2024 09:00:37 +0000

̽��ֱ��study, published today in Nature Communications, showed that the incidence of arterial thromboses, such as heart attacks and strokes, was up to 10% lower in the 13 to 24 weeks after the first dose of a COVID-19 vaccine. Following a second dose, the incidence was up to 27% lower after receiving the AstraZeneca vaccine and up to 20% lower after the Pfizer/Biotech vaccine.

̽��ֱ��incidence of common venous thrombotic events – mainly pulmonary embolism and lower limb deep venous thrombosis – followed a similar pattern.

Research led by the Universities of Cambridge, Bristol and Edinburgh and enabled by the British Heart Foundation (BHF) Data Science Centre at Health Data Research UK analysed de-identified health records from 46 million adults in England between 8 December 2020 and 23 January 2022. Data scientists compared the incidence of cardiovascular diseases after vaccination with the incidence before or without vaccination, during the first two years of the vaccination programme.

Co-first author Dr Samantha Ip, Research Associate at the Department of Public Health and Primary Care, ̽��ֱ�� of Cambridge, said: “We studied COVID-19 vaccines and cardiovascular disease in nearly 46 million adults in England and found a similar or lower incidence of common cardiovascular diseases, such as heart attacks and strokes, following each vaccination than before or without vaccination. This research further supports the large body of evidence on the safety of the COVID-19 vaccination programme, which has been shown to provide protection against severe COVID-19 and saved millions of lives worldwide.”

Previous research found that the incidence of rare cardiovascular complications is higher after some COVID-19 vaccines. For example, incidence of myocarditis and pericarditis have been reported following mRNA-based vaccines such as the Pfizer/Biotech vaccine, and vaccine-induced thrombotic thrombocytopenia following adenovirus-based vaccines such as the AstraZeneca vaccine. This study supports these findings, but importantly it did not identify new adverse cardiovascular conditions associated with COVID-19 vaccination and offers further reassurance that the benefits of vaccination outweigh the risk.

Incidence of cardiovascular disease is higher after COVID-19, especially in severe cases. This may explain why incidence of heart attacks and strokes is lower in vaccinated people compared with unvaccinated people, but further explanations are beyond the scope of this study.

Professor William Whiteley, Associate Director at the BHF Data Science Centre and Professor of Neurology and Epidemiology at the ̽��ֱ�� of Edinburgh, said: “ ̽��ֱ��COVID-19 vaccination programme rollout began strongly in the UK, with over 90% of the population over the age of 12 vaccinated with at least one dose by January 2022.

“This England-wide study offers patients reassurance of the cardiovascular safety of first, second and booster doses of COVID-19 vaccines. It demonstrates that the benefits of second and booster doses, with fewer common cardiovascular events include heart attacks and strokes after vaccination, outweigh the very rare cardiovascular complications.”

̽��ֱ��research team used de-identified linked data from GP practices, hospital admissions and death records, analysed in a secure data environment provided by NHS England.

Co-last author Dr Venexia Walker, Research Fellow at the ̽��ֱ�� of Bristol, said: “Given the critical role of COVID-19 vaccines in protecting people from COVID-19, it is important we continue to study the benefits and risks associated with them. ̽��ֱ��availability of population-wide data has allowed us to study different combinations of COVID-19 vaccines and to consider rare cardiovascular complications. This would not have been possible without the very large data that we are privileged to access and our close cross-institution collaborations.”

Reference
Ip, S et al. Cohort study of cardiovascular safety of different COVID-19 vaccination doses among 46 million adults in England. Nat Comms; 31 Jul 2024; DOI: 10.1038/s41467-024-49634-x

Adapted from a press release from Health Data Research UK

̽��ֱ��incidence of heart attacks and strokes was lower after COVID-19 vaccination than before or without vaccination, according to a new study involving nearly the whole adult population of England.

This research further supports the large body of evidence on the effectiveness of the COVID-19 vaccination programme, which has saved millions of lives worldwide

Samantha Ip

Paul_McManus

Vial of the AstraZeneca COVID-19 vaccine

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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New vaccine effective against coronaviruses that haven’t even emerged yet

jg533 — Mon, 06 May 2024 09:00:25 +0000

This is a new approach to vaccine development called ‘proactive vaccinology’, where scientists build a vaccine before the disease-causing pathogen even emerges.

̽��ֱ��new vaccine works by training the body’s immune system to recognise specific regions of eight different coronaviruses, including SARS-CoV-1, SARS-CoV-2, and several that are currently circulating in bats and have potential to jump to humans and cause a pandemic.

Key to its effectiveness is that the specific virus regions the vaccine targets also appear in many related coronaviruses. By training the immune system to attack these regions, it gives protection against other coronaviruses not represented in the vaccine – including ones that haven’t even been identified yet.

For example, the new vaccine does not include the SARS-CoV-1 coronavirus, which caused the 2003 SARS outbreak, yet it still induces an immune response to that virus.

“Our focus is to create a vaccine that will protect us against the next coronavirus pandemic, and have it ready before the pandemic has even started,” said Rory Hills, a graduate researcher in the ̽��ֱ�� of Cambridge’s Department of Pharmacology and first author of the report.

He added: “We’ve created a vaccine that provides protection against a broad range of different coronaviruses – including ones we don’t even know about yet.”

̽��ֱ��results are published today in the journal Nature Nanotechnology.

“We don’t have to wait for new coronaviruses to emerge. We know enough about coronaviruses, and different immune responses to them, that we can get going with building protective vaccines against unknown coronaviruses now,” said Professor Mark Howarth in the ̽��ֱ�� of Cambridge’s Department of Pharmacology, senior author of the report.

He added: “Scientists did a great job in quickly producing an extremely effective COVID vaccine during the last pandemic, but the world still had a massive crisis with a huge number of deaths. We need to work out how we can do even better than that in the future, and a powerful component of that is starting to build the vaccines in advance.”

̽��ֱ��new ‘Quartet Nanocage’ vaccine is based on a structure called a nanoparticle – a ball of proteins held together by incredibly strong interactions. Chains of different viral antigens are attached to this nanoparticle using a novel ‘protein superglue’. Multiple antigens are included in these chains, which trains the immune system to target specific regions shared across a broad range of coronaviruses.

This study demonstrated that the new vaccine raises a broad immune response, even in mice that were pre-immunised with SARS-CoV-2.

̽��ֱ��new vaccine is much simpler in design than other broadly protective vaccines currently in development, which the researchers say should accelerate its route into clinical trials.

̽��ֱ��underlying technology they have developed also has potential for use in vaccine development to protect against many other health challenges.

̽��ֱ��work involved a collaboration between scientists at the ̽��ֱ�� of Cambridge, the ̽��ֱ�� of Oxford, and Caltech. It improves on previous work, by the Oxford and Caltech groups, to develop a novel all-in-one vaccine against coronavirus threats. ̽��ֱ��vaccine developed by Oxford and Caltech should enter Phase 1 clinical trials in early 2025, but its complex nature makes it challenging to manufacture which could limit large-scale production.

Conventional vaccines include a single antigen to train the immune system to target a single specific virus. This may not protect against a diverse range of existing coronaviruses, or against pathogens that are newly emerging.

̽��ֱ��research was funded by the Biotechnology and Biological Sciences Research Council.

Reference: Hills, R A et al: ‘Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.’ Nature Nanotechnology, May 2024. DOI: 10.1038/s41565-024-01655-9

Researchers have developed a new vaccine technology that has been shown in mice to provide protection against a broad range of coronaviruses with potential for future disease outbreaks - including ones we don’t even know about

Our focus is to create a vaccine that will protect us against the next coronavirus pandemic, and have it ready before the pandemic has even started.

Rory Hills

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Syringe and vaccine bottle

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Researchers redesign future mRNA therapeutics to prevent potentially harmful immune responses

jg533 — Wed, 06 Dec 2023 16:02:31 +0000

mRNA - or ‘messenger ribonucleic acid’ - is the genetic material that tells cells in the body how to make a specific protein. Researchers from the Medical Research Council (MRC) Toxicology Unit have discovered that the cellular machinery that ‘reads’ mRNAs ‘slips’ when confronted with repeats of a chemical modification commonly found in mRNA therapeutics. In addition to the target protein, these slips lead to the production of ‘off-target’ proteins triggering an unintended immune response.

mRNA vaccines are considered game-changing. They have been used to control the COVID-19 pandemic and are already proposed to treat various cancers, cardiovascular, respiratory, and immunological diseases in the future.

This revolutionary class of therapeutics was made possible in part through the work of biochemist Katalin Karikó and immunologist Drew Weissman. They demonstrated that by adding chemical modifications to the bases – the building blocks of mRNA – the synthetic mRNAs could bypass some of our body’s immune defences allowing a therapeutic to enter the cell and exert its effects. This discovery led to their award of the Nobel Prize in Physiology and Medicine in 2023.

̽��ֱ��latest developments, led by biochemist Professor Anne Willis and immunologist Dr James Thaventhiran from the MRC Toxicology Unit at the ̽��ֱ�� of Cambridge, build upon previous advances to ensure the prevention of any safety issues linked with future mRNA-based therapeutics. Their report was published on 6 December in the journal Nature.

̽��ֱ��researchers identified that bases with a chemical modification called N1-methylpseudouridine – which are currently contained in mRNA therapies – are responsible for the ‘slips’ along the mRNA sequence.

In collaboration with researchers at the Universities of Kent, Oxford and Liverpool, the MRC Toxicology Unit team tested for evidence of the production of ‘off-target’ proteins in people who received the mRNA Pfizer vaccine against COVID-19. They found an unintended immune response occurred in one third of the 21 patients in the study who were vaccinated – but with no ill-effects, in keeping with the extensive safety data available on these COVID-19 vaccines.

̽��ֱ��team then redesigned mRNA sequences to avoid these ‘off-target’ effects, by correcting the error-prone genetic sequences in the synthetic mRNA. This produced the intended protein. Such design modifications can easily be applied to future mRNA vaccines to produce their desired effects while preventing hazardous and unintended immune responses.

“Research has shown beyond doubt that mRNA vaccination against COVID-19 is safe. Billions of doses of the Moderna and Pfizer mRNA vaccines have been safely delivered, saving lives worldwide,” said Dr James Thaventhiran from the MRC Toxicology Unit, joint senior author of the report.

He added: “We need to ensure that mRNA vaccines of the future are as reliable. Our demonstration of ‘slip-resistant’ mRNAs is a vital contribution to future safety of this medicine platform.”

“These new therapeutics hold much promise for the treatment of a wide range of diseases. As billions of pounds flow into the next set of mRNA treatments, it is essential that these therapeutics are designed to be free from unintended side-effects,” said Professor Anne Willis, Director of the MRC Toxicology Unit and joint senior author of the report.

Thaventhiran, who is also a practising clinician at Addenbrooke’s hospital, said: “We can remove the error-prone code from the mRNA in vaccines so the body will make the proteins we want for an immune response without inadvertently making other proteins as well. ̽��ֱ��safety concern for future mRNA medicines is that mis-directed immunity has huge potential to be harmful, so off-target immune responses should always be avoided.”

Willis added: “Our work presents both a concern and a solution for this new type of medicine, and result from crucial collaborations between researchers from different disciplines and backgrounds. These findings can be implemented rapidly to prevent any future safety problems arising and ensure that new mRNA therapies are as safe and effective as the COVID-19 vaccines.”

Using synthetic mRNA for therapeutic purposes is attractive because it is cheap to produce, so can address substantial health inequalities across the globe by making these medicines more accessible. Moreover, synthetic mRNAs can be changed rapidly – for example to create a new COVID-19 variant vaccine.

In the Moderna and Pfizer COVID-19 vaccines, synthetic mRNA is used to enable the body to make the spike protein from SARS-CoV-2. ̽��ֱ��body recognises the viral proteins generated by mRNA vaccines as foreign and generates protective immunity. This persists, and if the body is later exposed to the virus its immune cells can neutralise it before it can cause serious illness.

̽��ֱ��cell’s decoding machinery is called a ribosome. It ‘reads’ the genetic code of both natural and synthetic mRNAs to produce proteins. ̽��ֱ��precise positioning of the ribosome on the mRNA is essential to make the right proteins because the ribosome ‘reads’ the mRNA sequence three bases at a time. Those three bases determine what amino acid is added next into the protein chain. Therefore, even a tiny shift in the ribosome along the mRNA will massively distort the code and the resulting protein.

When the ribosome is confronted with a string of these modified bases called N1-methylpseudouridine in the mRNA, it slips around 10% of the time causing the mRNA to be misread and unintended proteins to be produced – enough to trigger an immune response. Removing these runs of N1-methylpseudouridine from the mRNAs prevents ‘off-target’ protein production.

This research was funded by the Medical Research Council and the Wellcome LEAP R3 programme, and supported by the NIHR Cambridge BRC.

Reference: Mulroney, T E et al: ‘(N)1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting.’ Nature, Dec 23. DOI: 10.1038/s41586-023-06800-3

Researchers have discovered that misreading of therapeutic mRNAs by the cell’s decoding machinery can cause an unintended immune response in the body. They have identified the sequence within the mRNA that causes this to occur and found a way to prevent ‘off-target’ immune responses to enable the safer design of future mRNA therapeutics.

As billions of pounds flow into the next set of mRNA treatments, it is essential that these therapeutics are designed to be free from unintended side-effects.

Anne Willis

Libre de droit/ Getty Images

Strand of mRNA

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New vaccine technology could protect from future viruses and variants

sc604 — Mon, 25 Sep 2023 15:10:32 +0000

̽��ֱ��vaccine antigen technology, developed by the ̽��ֱ�� of Cambridge and spin-out DIOSynVax in early 2020, provided protection against all known variants of SARS-CoV-2 – the virus that causes COVID-19 – as well as other major coronaviruses, including those that caused the first SARS epidemic in 2002.

̽��ֱ��studies in mice, rabbits and guinea pigs – an important step before beginning human clinical trials, currently underway in Southampton and Cambridge – found that the vaccine candidate provided a strong immune response against a range of coronaviruses by targeting the parts of the virus that are required for replication. ̽��ֱ��vaccine candidate is based on a single digitally designed and immune-optimised antigen.

Even though the vaccine was designed before the emergence of the Alpha, Beta, Gamma, Delta and Omicron variants of SARS-CoV-2, it provided a strong protection against all of these and against more recent variants, suggesting that vaccines based on DIOSynVax antigens may also protect against future SARS-CoV-2 variants.

DIOSynVax (Digitally Immune Optimised Synthetic Vaccines) uses a combination of computational biology, protein structure, immune optimisation, and synthetic biology to maximise and widen the spectrum of protection that vaccines can provide against global threats including existing and future virus outbreaks. Its vaccine candidates can be deployed in a variety of vaccine delivery and manufacturing platforms. ̽��ֱ��results are reported in the journal Nature Biomedical Engineering.

Since the SARS outbreak in 2002, coronavirus ‘spillovers’ from animals to humans have been a threat to public health, and require vaccines that provide broad-based protection. “In nature, there are lots of these viruses just waiting for an accident to happen,” said Professor Jonathan Heeney from Cambridge’s Department of Veterinary Medicine, who led the research. “We wanted to come up with a vaccine that wouldn’t only protect against SARS-CoV-2, but all its relatives.”

All currently available vaccines, such as the seasonal flu vaccine and existing Covid-19 vaccines, are based on virus strains or variants that arose at some point in the past. “However, viruses are mutating and changing all the time,” said Heeney. “Current vaccines are based on a specific isolate or variant that occurred in the past, it’s possible that a new variant will have arisen by the time we get to the point that the vaccine is manufactured, tested and can be used by people.”

Heeney’s team has been developing a new approach to coronavirus vaccines, by targeting their ‘Achilles heel’. Instead of targeting just the spike proteins on the virus that change to evade our immune system, the Cambridge vaccine targets the critical regions of the virus that it needs to complete its virus life cycle. ̽��ֱ��team identifies these regions through computer simulations and selecting conserved structurally engineered antigens. “This approach allows us to have a vaccine with a broad effect that viruses will have trouble getting around,” said Heeney.

Using this approach, the team identified a unique antigen structure that gave a broad-based immune responses against different Sarbeco coronaviruses, the large group of SARS and SARS-CoV-2 related viruses that occur in nature. ̽��ֱ��optimised antigen is compatible with all vaccine delivery systems: the team administered it as a DNA immunogen (in collaboration with the ̽��ֱ�� of Regensburg), a weakened version of a virus (Modified Vaccinia Ankara, supported by ProBiogen), and as an mRNA vaccine (in collaboration with Ethris). In all cases, the optimised antigen generated a strong immune response in mice, rabbits and guinea pigs against a range of coronaviruses. Based on a strong safety profile, the "first-in-human" clinical trials are ongoing at Southampton and Cambridge NIHR Clinical Research Facilities. ̽��ֱ��last booster immunisations will conclude by the end of September.

“Unlike current vaccines that use wild-type viruses or parts of viruses that have caused trouble in the past, this technology combines lessons learned from nature’s mistakes and aims to protect us from the future,” said Heeney. “These optimised synthetic antigens generate broad immune responses, targeted to the key sites of the virus that can’t change easily. It opens the door for vaccines against viruses that we don’t yet know about. This is an exceptionally different vaccine technology – it’s a real turning point.”

̽��ֱ��research was initially funded by the DHSC UK Vaccine Network programme and later in part by the Innovate UK DIOS-CoVax programme. ̽��ֱ��DIOSynVax pipeline includes vaccine candidates for influenza viruses, haemorrhagic fever viruses, and coronaviruses including SARS-CoV-2, the latter of which is currently in clinical trials.

DIOSynVax is a spin-out company from the ̽��ֱ�� of Cambridge, established in 2017 with the support of Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm. Jonathan Heeney is the Professor of Comparative Pathology at the ̽��ֱ�� of Cambridge, and a Fellow at Darwin College.

Reference:
Sneha Vishwanath et al. ‘A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses.’ Nature Biomedical Engineering (2023). DOI: 10.1038/s41551-023-01094-2

Studies of a ‘future-proof’ vaccine candidate have shown that just one antigen can be modified to provide a broadly protective immune response in animals. ̽��ֱ��studies suggest that a single vaccine with combinations of these antigens – a substance that causes the immune system to produce antibodies against it – could protect against an even greater range of current and future coronaviruses.

This is an exceptionally different vaccine technology – it’s a real turning point

Jonathan Heeney

Uma Shankar sharma via Getty Images

Virus mutation

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cambridge ̽��ֱ��’s needle-free coronavirus vaccine begins clinical trials in home city

cjb250 — Mon, 24 Apr 2023 07:00:20 +0000

̽��ֱ��vaccine – known as DIOS-CoVax – has been developed by Professor Jonathan Heeney at the ̽��ֱ�� of Cambridge and spin-out company DIOSynVax. It is envisaged as a booster targeting SARS-CoV-2 and relatives that threaten future coronavirus pandemics.

This next generation vaccine is administered through a needle-free ‘injection’ – a blast of air that delivers it into the skin. It has already been part of safety trials conducted at the NIHR Southampton Clinical Research Facility, but now recruitment is being expanded to Cambridge.

Professor Heeney said: “We’re excited to be bringing our vaccine ‘home’ and are looking to recruit healthy volunteers to help in this crucial stage of development towards what we hope will eventually become a universal coronavirus vaccine.

“Our vaccine is innovative, both in terms of how it aims to protect against thevirus responsible for our current pandemic and future coronaviruses, but also in how it is delivered. If you’re someone who hates needles, our vaccine could be the answer as it’s delivered by a jet of air, not a needle.”

If the clinical trials are successful, the vaccine could be scaled up and manufactured as a powder to boost global vaccination efforts, particularly in low- and middle-income countries.

̽��ֱ��clinical trials team at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust is looking for healthy volunteers aged 18-50 to take part in the study. Volunteers will receive payment for their time, and participation on the trial will last around 12 months with volunteers attending 11 visits. To find out more, contact the Project Management Team at cuh.dioscovaxtrial@nhs.net.

Funding for the development of the vaccine has come from Innovate UK, part of UK Research and Innovation.

DIOSynVax is a spin-out company from the ̽��ֱ�� of Cambridge, established in 2017 with the support of Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm. Professor Heeney is a Fellow at Darwin College, Cambridge.

Trials of a novel needle-free coronavirus vaccine begin in Cambridge

Lloyd Mann ( ̽��ֱ�� of Cambridge)

Vaccine being administered by needle-free injection into a volunteer's arm

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Referrals to long COVID clinic fell by 79% following roll-out of the vaccine

cjb250 — Thu, 06 Oct 2022 07:00:15 +0000

According to the Office of National Statistics, in July this year an estimated 2 million people in the UK were living with self-reported long COVID – that is, symptoms continuing for more than four weeks after their first suspected coronavirus (COVID-19) infection. Patients report symptoms including fatigue, muscle aches, memory problems and shortness of breath more than six months post-acute COVID-19, and a significant number of patients have not fully recovered two years since the initial infection.

Two recent studies have suggested that vaccination strongly reduced long COVID symptoms one-to-three months after infection, but another study using a cohort of US Army Veterans suggested a more modest, 15% reduction at six months.

In May 2020, Addenbrooke’s Hospital, part of Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH), set up a long COVID clinic, with patients referred to the clinic based on a number of criteria, one of which is symptoms duration of at least five months. These patients tend to be those on the severe end of the symptom spectrum, having been referred following assessment by a team that includes a GP, mental health practitioners, physio and occupational therapists amongst other specialists.

Researchers at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) at the ̽��ֱ�� of Cambridge and CUH, analysed data from the clinic and found a 79% drop in the number of patients being referred to the clinic from August 2021 to June 2022, compared to August 2020 to July 2021. ̽��ֱ��decrease began five months after people started receiving second doses of COVID-19 vaccines.

Six-month moving averages fell from around 10 referrals per month to just one or two referrals per month. This effect has so far been sustained until at least June 2022, despite four times more cases per month of acute COVID-19 in England across the same time periods.

Dr Ben Krishna from the ̽��ֱ�� of Cambridge said: “Long COVID can have a significant impact on an individual’s life, and the large number of patients still experiencing symptoms many months after infection is placing additional strain on our healthcare services.

“We know that rollout of the vaccines has had a major impact on the number and severity of COVID infections, and evidence from our clinic suggests that it has also played an important role in reducing the rates of the most severe long COVID cases.”

̽��ֱ��researchers say that it is possible – but unlikely – that the emergence of the Delta variant may also have affected long COVID rates. However, the observed reduction in long COVID rates in August 2021 was from patients experiencing symptoms for five months, which they say would suggest a change beginning in March 2021. This correlates well with the second doses of vaccination in the UK, but the Delta wave did not begin until April 2021.

̽��ֱ��team say they also cannot rule out prior infections providing immunity that protects against long COVID from reinfections; however, primary infections were more common than reinfections around March-April 2021.

̽��ֱ��team observed no changes in symptoms between those referred for long COVID before or after vaccination for any of the major symptoms such as fatigue (73% pre-vaccination vs 76% post vaccination) and shortness of breath (18% pre-vaccination vs 23% post-vaccination).

It is not yet clear what level of immunity is required to protect against long COVID, say the researchers. As immunity wanes over time, booster shots – including variant-specific booster shots – may be necessary to minimise long COVID risk.

Dr Nyaradzai Sithole from CUH said: “As the virus continues to circulate and infect – and in many cases, re-infect – people, it’s important that everyone is up-to-date with their vaccinations. This will not only help prevent, or at least lessen, their primary COVID infection, but should reduce their risk of long COVID. But whether with the emergence of new variants we will begin to see an uptick in the number of cases of long COVID remains to be seen.”

̽��ֱ��study is published in Clinical Infectious Diseases.

̽��ֱ��research as funded by the Addenbrooke’s Charitable Trust and the National Institute for Health and Care Research (NIHR), with support from the NIHR Cambridge Biomedical Research Centre.

Reference
Krishna, B et al. Reduced incidence of Long COVID referrals to the Cambridge ̽��ֱ�� Teaching Hospital Long COVID clinic. Clinical Infectious Diseases; 1 Aug 2022; DOI: 10.1093/cid/ciac630

Referrals to Cambridge’s long COVID clinic fell dramatically in the period August 2021 to June 2022, which researchers say is likely due to the successful rollout of the vaccine.

We know that rollout of the vaccines has had a major impact on the number and severity of COVID infections, and evidence from our clinic suggests that it has also played an important role in reducing the rates of the most severe long COVID cases

Ben Krishna

pearson0612

Model of coronavirus and hypodermic needle

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cambridge vaccine expert in $42million partnership to develop 'future-proofed' coronavirus vaccines

cjb250 — Tue, 08 Mar 2022 10:00:33 +0000

̽��ֱ��investment from the Coalition for Epidemic Preparedness Innovations (CEPI) will support the development of an mRNA vaccine. DIOSynVax, led by Professor Jonathan Heeney, Head of the Laboratory of Viral Zoonotics, ̽��ֱ�� of Cambridge, will design and select the lead antigen through proof-of-concept preclinical studies, and undertake initial clinical development through Phase I/II studies.

DIOSynVax uses the combination of protein structure, computational biology and immune-optimisation to maximise the protection that vaccines can provide against global threats including existing and future virus outbreaks. Its vaccine candidates can be deployed in a variety of vaccine delivery and manufacturing platforms.

̽��ֱ��DIOSynVax pipeline includes vaccine candidates for haemorrhagic fever viruses, influenza, and SARS-CoV-2, the latter of which is currently in clinical trials.

If DIOSynVax’s novel antigen design is successfully deployed using the intended mRNA platform, it could potentially be used to enable rapid development of vaccines against so-called Disease X – unknown pathogens with pandemic potential that have yet to emerge.

Professor Jonathan Heeney, Cambridge, said: "We are excited to be working with CEPI on its ground-breaking mission to leverage revolutionary science and technology to outmanoeuvre and minimise future pandemic threats.

"Our approach is to be ahead of the next pandemic - to deliver custom designed, immune selected vaccine antigens – which is ideal to prevent diseases caused by complex viruses such as the large and diverse family of coronaviruses. If successful, it will result in a safe, affordable NextGen vaccine for widespread use.”

CEPI, DIOSynVax and the ̽��ֱ�� of Cambridge are committed to enabling global equitable access to the vaccines developed through this partnership. Under the terms of the funding agreement, DIOSynVax has committed to achieving equitable access to the outputs of this project.

Dr Richard Hatchett, CEO of CEPI, said: “ ̽��ֱ��UK Government and the country’s world-leading scientific institutions have been pivotal to the global response to COVID-19. From the development of the CEPI-supported Oxford/AstraZeneca vaccine – which is used in more countries than any other – to the ground-breaking Recovery trial to evaluate life-saving treatments like dexamethasone, British science has played a leading role in protecting the world from COVID-19.

“I am excited to further strengthen CEPI’s strong ties to British science through this partnership with DIOSynVax, Cambridge, to develop a vaccine with the potential to protect against variants of SARS-CoV-2 and other Betacoronaviruses in the future. Coronaviruses have now proven their pandemic potential, so it’s imperative for global health security that we invest in R&D now to future-proof the world against the threat of coronaviruses.”

̽��ֱ��announcement was made today at the Global Pandemic Preparedness Summit, which brings together a unique mix of leaders across governments, international agencies, science and academia, industry, philanthropy, and civil society to explore how to collectively prepare for future viral threats and mobilise critical resources and political support for CEPI’s work.

DIOSynVax is a spin-out company from the ̽��ֱ�� of Cambridge, set up in 2017 with the support of Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm.

Professor Heeney is a Fellow at Darwin College, Cambridge.

Adapted from a press release from CEPI

Prime Minister Boris Johnson announced that DIOSynVax, a biotech spinout of the ̽��ֱ�� of Cambridge, will receive $42 million (about £32 million) to develop a vaccine candidate that could provide protection against both existing and future variants of SARS-CoV-2 – the virus that causes COVID-19 – as well as other major coronaviruses, including those that cause SARS and MERS.

Our approach is to be ahead of the next pandemic - to deliver custom designed, immune selected vaccine antigens – which is ideal to prevent diseases caused by complex viruses such as the large and diverse family of coronaviruses

Jonathan Heeney

Nick Saffell ( ̽��ֱ�� of Cambridge)

Professor Jonathan Heeney

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Omicron may be significantly better at evading vaccine-induced immunity, but less likely to cause severe disease

cjb250 — Mon, 20 Dec 2021 15:37:40 +0000

As the SARS-CoV-2 virus replicates and spreads, errors in its genetic code can lead to changes in the virus. On 26 November 2021, the World Health Organization designated the variant B.1.1.529, first identified in South Africa, a variant of concern, named Omicron. ̽��ֱ��variant carries a large number of mutations, leading to concern that it will leave vaccines less effective at protecting against infection and illness.

Working in secure conditions, a team led by Professor Ravi Gupta at the Cambridge Institute of Therapeutic Immunology and Infectious Disease, ̽��ֱ�� of Cambridge, created synthetic viruses – known as ‘pseudoviruses’ – that carried key mutations found in the Delta and Omicron strains. They used these to study the virus’s behaviour.

̽��ֱ��team, which included collaborators from Japan, including Dr Kei Sato of the ̽��ֱ�� of Tokyo, has released its data ahead of peer review* because of the urgent need to share information relating to the pandemic, and particularly the new Omicron variant.

Professor Gupta and colleagues tested the pseudoviruses against blood samples donated to the NIHR COVID-19 BioResource. ̽��ֱ��blood samples were from vaccinated individuals who had received two doses of either the AstraZeneca (ChAdOx-1) or Pfizer (BNT162b2) vaccines.

On average, Omicron required around a ten-fold increase in the concentration of serum antibody in order to neutralise the virus, compared to Delta. Of particular concern, antibodies from the majority of individuals who had received two doses of the AstraZeneca vaccine were unable to neutralise the virus. ̽��ֱ��data were confirmed in live virus experiments.

Reassuringly, however, following a third dose of the Pfizer vaccine, both groups saw a significant increase in neutralisation.

Professor Gupta said: “ ̽��ֱ��Omicron variant appears to be much better than Delta at evading neutralising antibodies in individuals who have received just two doses of the vaccine. A third dose ‘booster’ with the Pfizer vaccine was able to overturn this in the short term, though we’d still expect a waning in immunity to occur over time.”

Spike proteins on the surface of SARS-CoV-2 bind to ACE2, a protein receptor found on the surface of cells in the lung. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. ̽��ֱ��virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

To see how effective Omicron is at entering our cells, the team used their pseudoviruses to infect cells in lung organoids – ‘mini-lungs’ that model parts of the lung. Despite having three mutations that were predicted to favour the spike cleavage, the researchers found the Omicron spike protein to be less efficient than the Delta spike at cleaving the ACE2 receptor and entering the lung cells.

In addition, once Omicron had entered the cells, it was also less able than Delta to cause fusion between cells, a phenomenon associated with impaired cell-to-cell spread. Fused cells are often seen in respiratory tissues taken following severe disease. Indeed, when the team used a live Omicron virus and compared it to Delta in a spreading infection experiment using lung cells, Omicron was significantly poorer in replication, confirming the findings regarding impaired entry.

Professor Gupta added: “We speculate that the more efficient the virus is at infecting our cells, the more severe the disease might be. ̽��ֱ��fact that Omicron is not so good at entering lung cells and that it causes fewer fused cells with lower infection levels in the lab suggests this new variant may cause less severe lung-associated disease.

“While further work is needed to corroborate these findings, overall, it suggests that Omicron’s mutations present the virus with a double-edged sword: it’s got better at evading the immune system, but it might have lost some of its ability to cause severe disease.”

However, Professor Gupta urged caution.

“Omicron still represents a major public health challenge. Individuals who have only received two doses of the vaccine – or worse, none at all – are still at significant risk of COVID-19, and some will develop severe disease. ̽��ֱ��sheer number of new cases we are seeing every day reinforces the need for everyone to get their boosters as quickly as possible.”

̽��ֱ��research was supported by Wellcome and the NIHR Cambridge Biomedical Research Centre.

Reference
Meng, B, et al. SARS-CoV-2 Omicron neutralising antibody evasion, replication and cell-cell fusion.

*Update: ̽��ֱ��research has now been peer-reviewed and is published in Nature as Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity (DOI: 10.1038/s41586-022-04474-x).

̽��ֱ��Omicron variant of SARS-CoV-2 may be significantly better than previous variants at evading vaccine-induced antibodies, according to new research from Cambridge – but preliminary evidence suggests it is less likely to cause severe COVID-19 illness in the lungs.

Omicron’s mutations present the virus with a double-edged sword: it’s got better at evading the immune system, but it might have lost some of its ability to cause severe disease

Ravi Gupta

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Omicron may be significantly better at evading vaccine-induced immunity, but less likely to cause severe disease